The Jackson Laboratory, Bar Harbor, ME 04609, USA.
J Neurophysiol. 2010 May;103(5):2470-81. doi: 10.1152/jn.00601.2009. Epub 2010 Mar 3.
Methyl-CpG binding protein 2 (MeCP2) is highly expressed in neurons in the vertebrate brain, and mutations of the gene encoding MeCP2 cause the neurodevelopmental disorder Rett syndrome. This study examines the role of MeCP2 in the development and function of thalamic GABAergic circuits. Whole cell recordings were carried out in excitatory neurons of the ventrobasal complex (VB) of the thalamus and in inhibitory neurons of the reticular thalamic nucleus (RTN) in acute brain slices from mice aged P6 through P23. At P14-P16, the number of quantal GABAergic events was decreased in VB neurons but increased in RTN neurons of Mecp2-null mice, without any change in the amplitude or kinetics of quantal events. There was no difference between mutant and wild-type mice in paired-pulse ratios of evoked GABAergic responses in the VB or the RTN. On the other hand, unitary responses evoked by minimal stimulation were decreased in the VB but increased in the RTN of mutants. Similar changes in the frequency of quantal events were observed at P21-P23 in both the VB and RTN. At P6, however, quantal GABAergic transmission was altered only in the VB not the RTN. Immunostaining of vesicular GABA transporter showed opposite changes in the number of GABAergic synaptic terminals in the VB and RTN of Mecp2-null mice at P18-P20. The loss of MeCP2 had no significant effect on intrinsic properties of RTN neurons recorded at P15-P17. Our findings suggest that MeCP2 differentially regulates the development of GABAergic synapses in excitatory and inhibitory neurons in the thalamus.
甲基化 CpG 结合蛋白 2（MeCP2）在脊椎动物大脑的神经元中高度表达，编码 MeCP2 的基因突变会导致神经发育障碍雷特综合征。本研究探讨了 MeCP2 在丘脑 GABA 能回路发育和功能中的作用。在从 P6 到 P23 的急性脑切片中，在丘脑腹侧基底复合体（VB）的兴奋性神经元和网状丘脑核（RTN）的抑制性神经元中进行全细胞膜片钳记录。在 P14-P16 时，Mecp2 缺失小鼠 VB 神经元中量子 GABA 能事件的数量减少，但 RTN 神经元中增加，而量子事件的幅度或动力学没有变化。在 VB 或 RTN 中，诱发 GABA 能反应的成对脉冲比在突变体和野生型小鼠之间没有差异。另一方面，在 VB 中最小刺激诱发的单位反应减少，但在 RTN 中增加。在 VB 和 RTN 中均观察到 P21-P23 时量子事件频率的相似变化。然而，在 P6 时，仅在 VB 而不是 RTN 中改变了量子 GABA 能传递。在 P18-P20 时，Mecp2 缺失小鼠 VB 和 RTN 中囊泡 GABA 转运蛋白的免疫染色显示 GABA 能突触末梢数量的相反变化。MeCP2 的缺失对 P15-P17 记录的 RTN 神经元的固有特性没有显著影响。我们的发现表明，MeCP2 差异调节丘脑兴奋性和抑制性神经元中 GABA 能突触的发育。
